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Fast Linkage Analysis with MOD Scores Using Algebraic Calculation

机译：使用代数计算的MOD分数快速链接分析

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Objective: As the mode of inheritance is often unknown for complex diseases, a MOD-score analysis, in which the parametric LOD score is maximized with respect to the trait-model parameters, can be a powerful approach in genetic linkage analysis. Because the calculation of the disease-locus likelihood is the most time-consuming step in a MOD-score analysis, we aimed to optimize this part of the calculation to speed up linkage analysis using the GENEHUNTER-MODSCORE software package. Methods: Our new algorithm is based on minimizing the effective number of inheritance vectors by collapsing them into classes. To this end, the disease-locus-likelihood contribution of each inheritance vector is represented and stored in its algebraic form as a symbolic sum of products of penetrances and disease-allele frequencies. Simulations were used to assess the speedup of our new algorithm. Results: We were able to achieve speedups ranging from 1.94 to 11.52 compared to the original GENEHUNTER-MODSCORE version, with higher speedups for larger pedigrees. When calculating p values, the speedup ranged from 1.69 to 10.36. Conclusion: Computation times for MOD-score analysis, involving the evaluation of many tested sets of trait-model parameters and p value calculation, have been prohibitively high so far. With our new algebraic algorithm, such an analysis is now feasible within a reasonable amount of time. (c) 2015 S. Karger AG, Basel
机译：目的：由于复杂疾病的遗传模式通常是未知的，因此针对特征模型参数最大化参数LOD得分的MOD评分分析可以成为遗传连锁分析的有效方法。由于疾病位置可能性的计算是MOD得分分析中最耗时的步骤，因此我们旨在优化这部分计算，以使用GENEHUNTER-MODSCORE软件包加快链接分析。方法：我们的新算法基于将继承向量折叠成类，从而将其有效数量最小化。为此，每个遗传载体的疾病位点可能性贡献都以代数形式表示并存储为外显率和疾病等位基因频率乘积的符号和。仿真用于评估我们新算法的加速。结果：与原始的GENEHUNTER-MODSCORE版本相比，我们能够实现1.94到11.52的加速比，对于更大的血统书来说，加速比更高。计算p值时，加速范围为1.69至10.36。结论：迄今为止，用于MOD得分分析的计算时间过长，令人难以置信，其中包括评估许多测试的特征模型参数集和p值计算。使用我们的新代数算法，现在可以在合理的时间内进行这种分析。 （c）2015 S.Karger AG，巴塞尔

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